6MUA

Crystal structure of Csm1-Csm4 subcomplex in the type III-A CRISPR-Csm interference complex

6MUA の概要

• エントリーDOI: 10.2210/pdb6mua/pdb
• 分子名称: Uncharacterized protein Csm1, Uncharacterized protein Csm4 (2 entities in total)
• 機能のキーワード: type iii-a crispr-cas system, csm1-csm4 subcomplex, immune system
• 由来する生物種: Thermococcus onnurineus; 詳細
• タンパク質・核酸の鎖数: 2
• 化学式量合計: 122095.66

構造登録者

Jia, N.,Patel, D.J. (登録日: 2018-10-22, 公開日: 2019-01-09, 最終更新日: 2023-10-11)

主引用文献

Jia, N.,Mo, C.Y.,Wang, C.,Eng, E.T.,Marraffini, L.A.,Patel, D.J.
Type III-A CRISPR-Cas Csm Complexes: Assembly, Periodic RNA Cleavage, DNase Activity Regulation, and Autoimmunity.
Mol. Cell, 73:264-, 2019

PubMed Abstract: Type ΙΙΙ CRISPR-Cas systems provide robust immunity against foreign RNA and DNA by sequence-specific RNase and target RNA-activated sequence-nonspecific DNase and RNase activities. We report on cryo-EM structures of Thermococcus onnurineus Csm binary, Csm-target RNA and Csm-target RNA ternary complexes in the 3.1 Å range. The topological features of the crRNA 5'-repeat tag explains the 5'-ruler mechanism for defining target cleavage sites, with accessibility of positions -2 to -5 within the 5'-repeat serving as sensors for avoidance of autoimmunity. The Csm3 thumb elements introduce periodic kinks in the crRNA-target RNA duplex, facilitating cleavage of the target RNA with 6-nt periodicity. Key Glu residues within a Csm1 loop segment of Csm adopt a proposed autoinhibitory conformation suggestive of DNase activity regulation. These structural findings, complemented by mutational studies of key intermolecular contacts, provide insights into Csm complex assembly, mechanisms underlying RNA targeting and site-specific periodic cleavage, regulation of DNase cleavage activity, and autoimmunity suppression.

PubMed: 30503773
DOI: 10.1016/j.molcel.2018.11.007

実験手法

X-RAY DIFFRACTION (2.91 Å)